The proposed research project involves the synthesis and pharmacological evaluation of agents which directly inhibit the human blood platelet thromboxane receptor. To date we have developed a series of azoprostanoic acids (in particular 13-azaprostanoic acid (13-APA)) which appear to specifically antagonize the action of thromboxane or endoperoxide at the receptor level. Experiments are proposed to further evaluate the selectivity of these agents relative to thromboxane receptor inhibition. In addition isotopically labeled derivatives and alkylating derivatives of the azoprostanoids will be synthesized to obtain information concerning the location and protein composition of the presumed platelet thromboxane receptor. Experiments are also outlined which will employ 13-APA (or other azaprostanoates) to investigate the role of thromboxane or endoperoxide in the induction of primary and secondary agregation; as well as to examine the potential effects of direct receptor inhibition on the formation of circulatory thrombi induced by arachidonic acid. Concomitant with the pharmacological evaluation of presently available agents, a synthetic program will be undertaken to develop more potent anagonists of thromboxane induced platelet aggregation. Such information will be of considerable value in establishing the molecular characteristics which confer receptor inhibitory activity.